Inhibiting the Anti-apoptotic Factor, BCL-2, at the Time of ART Initiation to Promote Apoptosis of HIV-infected Cells and Restrict the Seeding of the HIV Reservoir (The INITIATE Study)

Exclusion Criteria

• •An individual who meets any of the following criteria will be excluded from participation in this study.
• •Current or previous use of a BCL-2 antagonist or other pro-apoptotic agent used as cancer therapy
• •Evidence of or strong suspicion that HIV infection was acquired during active PrEP use
• •Any concomitant disease where venetoclax treatment is indicated
• •Current use of any moderate or strong CYP3A4 inhibitors (such as ketoconazole, voriconazole, posaconazole, itraconazole, ritonavir, cobicistat and clarithromycin)
• •Current use of any HIV protease inhibitor (due to CYP3A4 inhibition)
• •Current use of any strong inhibitor of the P-gp drug efflux pump (this includes cobicistat, ritonavir, azithromycin and clarithromycin)
• •Current use of P-gp substrates with narrow therapeutic index (such as such as digoxin, tacrolimus, cyclosporine, sirolimus, dabigatran, colchicine, loperamide)
• •Current use of strong or moderate CYP3A4 inducers (such as carbamazepine, phenytoin, rifampicin, St. John's wort, bosentan, efavirenz and etravirine); intermittent use of moderate CYP3A4 inducers such as modafinil and nafcillin may be used but should be avoided as much as possible
• •Receipt of immunomodulating agents (excluding immunisation) or systemic chemotherapeutic agents within 28 days prior to study entry
• •Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study
• •Known hypersensitivity to the components of venetoclax or its analogues
• •Any evidence of an active AIDS-defining opportunistic infection
• •Individuals who intend to modify their ART regimen within the study period
• •Current or recent gastrointestinal disease or gastrointestinal surgery that may impact the absorption of the investigational drug
• •Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy or procedures
• •Unable or unwilling to adhere to protocol procedures
• •History of malignancy or transplantation, excluding adequately treated basal cell carcinoma
• •Co-infection with hepatitis B defined as HBsAg-positive or Hepatitis C defined as HCV-RNA positive (Individuals with prior hepatitis B or C infection that is now cleared are eligible for enrolment)
• •For individuals with isolated anti-HBcAb (cleared hepatitis B), the chosen ART regimen must include TDF or TAF
• •Impaired liver function with AST or ALT \>3 times upper limit of normal
• •Severe hepatic impairment (Class C) as determined by Child-Pugh classification
• •Impaired renal function with estimated creatinine clearance (eGFR) \<50 mL/min
• •Significant cardiac dysfunction